This project investigates the roles of autonomic nervous system (ANS) activity, attention and information processing and their interrelationships in the pathology, etiology, and prognosis of various psychiatric disorders and studies biological and psychological processes related to AND activity and attention. ANS activity is assessed by peripheral measures such as skin conductance, heart rate, and skin temperature. Subjects are tested under conditions of rest, presentation of tones, and performance on various tasks. Biological mechanisms are investigated by correlating these variables with enzyme activity, neuropeptides, and levels of biogenic amines and their metabolites and with brain dysfunction as revealed by CT, MRI, and PET scans. Recent and current work: 1) in schizophrenic patients we found that the atypical neuroleptic clozapine markedly attenuates ANS activity compared to a typle neuroleptic and placebo but had about the same effect on attentionas the neuroleptic. 2) Young adults who are at familial risk for affective disorder were hyperresponsive in skin conductance reactions to mild stress, and these showed atypical lateralization. These subjects also showed an atypical increase in self-ratings of depression along with a normal increase in anxiety, and they showed atypically strong correlations between state and trait anxiety and ANS activity not seen in controls. The results support a sensitization model of the development of affective disorders. 3) Parental "Expressed Emotion", an index of criticism and/or overinvolvement, is related, especially in fathers, to high skin conductance activity in obsessive-compulsive children. 4) Adolescents with Childhood Schizophrenia are being tested on the same protocol used with children with various other diagnoses. 5) Subjects with closed head injuries and with focal brain lesions are being tested on the same protocols used with the schizophrenics in part and to explore the neurobiology of schizophrenia and in part to study central determinants of ANS reactions.